KRAS G13

The pan-RAS mRNA vaccine demonstrates structural stability and strong immunogenic potential for PDAC. Synergistic immune activation with R848 may enhance anti-tumor efficacy, warranting experimental validation and toxicity assessment for clinical translation.

This patent provides novel macrocycle compounds that inhibit key mutants (G12D/G13D) of the KRAS oncogene, which is the most frequently mutated in human cancers. These compounds, along with their pharmaceutical compositions and protein complexes, are intended for the treatment of cancers driven by these mutations.

We conclude that ddPCR testing of plasma supernatant achieved high overall agreement with tumour KRASmt status. There was varying abundance of KRAS detected in the plasma fractions.

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Feb 2027

P1, N=750, Active, not recruiting, Eli Lilly and Company | Recruiting --> Active, not recruiting

Across a CRC panel that included SNU-C5/WT and its 5-fluorouracil- and oxaliplatin-resistant derivatives, HT-29 (KRAS-wild-type), and HCT-8 and LoVo (KRAS-mutant), co-immunoprecipitation showed that PrPC forms complexes with the 37/67 kDa laminin receptor (RPSA), with PrPC-RPSA association particularly increased in KRAS-mutant HCT-8 and LoVo cells. Taken together, these findings suggest that extracellular PrPC supports RAS-AKT signaling, proliferation, and tumor-associated angiogenesis in KRAS-mutant colorectal cancer, and that PrPC neutralization additively enhances 5-fluorouracil activity in KRAS-mutant models. The data provide a preclinical basis for evaluating PrPC antibodies in combination with fluoropyrimidine-based regimens in patients with KRAS-mutant CRC.

In this phase I study, we test a pooled synthetic long peptide vaccine targeting the six KRAS mutations (G12V, G12A, G12R, G12C, G12D, G13D) with ipilimumab and nivolumab in resected pancreatic adenocarcinoma. The vaccine also generates cross-reactive T cells that recognize more than one mutant KRAS antigen. These findings support the safety and diverse anti-tumor immunity of mutant KRAS vaccines (NCT04117087).

P=N/A, N=12, Not yet recruiting, Cancer Hospital of Chinese Academy of Medical Sciences; Cancer Hospital of Chinese Academy of Medical Sciences

P1, N=32, Not yet recruiting, Zhejiang Cancer Hospital; Shanghai Ruihongdi Pharmaceutical Co., LTD

The cancer was refractory to regimens extrapolated from rectal cancer management (capecitabine with oxaliplatin, and irinotecan). Pelvic recurrence and osseous metastases were clearly radiosensitive. Tumor molecular profile showed microsatellite stable cancer with KRAS p.G13D and TP53 p.C176W mutations.

In conclusion, no significant associations between KRAS-G12 and overall survival were found for TAS-102 or TAS-Bev. Further research is needed to assess the impact of these mutations on combined TAS-Bev therapy prior to any clinical application.